PROJECT SUMMARY/ABSTRACT McLean Hospital Project 4 The main goal of the proposed project, entitled “Modulation of the OCD neural network by conventional treatment,” is to study how conventional interventions for severe OCD – intensive exposure and response prevention (ERP) therapy and standard of care medication management – affect the putative OCDnet to further our understanding of how commonly available, efficacious treatments for OCD impact neural circuits involved in avoidance and aversive uncertainty. To achieve this goal, P4 will identify abnormalities in the vlPFC, rACC, insula, dACC, OFC and rostral striatum that track with performance on the PAAT and clinical symptom reports in individuals with OCD as they receive intensive treatment and undergo changes in illness burden over time. The project will follow 95 individuals with OCD using intensive longitudinal assessment of brain and behavior over the typical ~8wk treatment course. P4 will build on our group’s operational experience performing serial MRI (functional and structural) and detailed serial clinical assessments in OCD, and our toolkit for intensive longitudinal assessment, currently deployed in other NIMH-funded data collection efforts and developed with members of Core C, to identify changes in the OCDnet, persistent avoidance (as measured on PAAT and with exploratory device-based measures), and clinical changes in OCD. Three sets of comprehensive study visits (before, during, and after treatment) with MRI and clinical assessments will provide illness trajectory information for probing relationships between changing constructs at a coarse timescale, complemented by low-burden, digital phenotyping to capture variation at intermediate and finer time scales. Elucidating the ways in which the putative OCDnet changes in relation to changes in clinical and therapeutic parameters will provide targets for new interventions for OCD and help understand how and in which individuals currently available treatments achieve their optimal therapeutic benefit.